Serotonin1A-receptor agonism attenuates the cocaine-induced increase in serotonin levels in the hippocampus and nucleus accumbens but potentiates hyperlocomotion: an in vivo microdialysis study

• Published in: Neuropharmacology 2003-04, Vol.44 (5), p.592-603
• Main Authors: MÜLLER, C. P, CAREY, R. J, SALLOUM, J. B, HUSTON, J. P
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Animals; Biological and medical sciences; Cocaine - pharmacology; Drug Synergism; Hippocampus - drug effects; Hippocampus - metabolism; Locomotion - drug effects; Locomotion - physiology; Male; Medical sciences; Microdialysis - methods; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Rats; Rats, Wistar; Receptors, Serotonin - metabolism; Receptors, Serotonin, 5-HT1; Serotonin - metabolism; Serotonin Receptor Agonists - pharmacology
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/s0028-3908(03)00046-7

The hippocampus and the nucleus accumbens (Nac) are important structures for the modulation of spontaneous locomotor activity. Both structures receive a serotonergic (5-HT) innervation. We have previously reported that the 5-HT(1A)-receptor antagonist WAY 100635 blocked cocaine-induced hyperactivity, while potentiating cocaine-induced 5-HT increases in the hippocampus and the Nac. In order to further investigate the relationship between extracellular 5-HT concentration and cocaine-induced behaviour, we used in vivo microdialysis to measure the effects of the 5-HT(1A)-receptor agonist 8-OH-DPAT on cocaine-induced changes in the extracellular 5-HT concentration in the hippocampus and the Nac and on behavioural activity. Following a pilot pretest in which we determined the lowest effective dose of 8-OH-DPAT for potentiating cocaine-induced hyperlocomotion, four groups of rats were given one of the following drug treatments: 8-OH-DPAT (0.2 mg/kg) and cocaine (10 mg/kg), saline and cocaine (10 mg/kg), 8-OH-DPAT (0.2 mg/kg) and saline, or saline and saline. The injections were administered i.p. and spaced 30 min apart. We found that the 5-HT(1A)-receptor agonist 8-OH-DPAT attenuated the cocaine-induced increases in 5-HT in the hippocampus and the Nac, but potentiated cocaine-induced hyperlocomotion. 5-HT metabolite measurements revealed a complex role for the 5-HT(1A)-receptor in the broad spectrum of cocaine's neurochemical effects. Altogether, these observations support an important role of the 5-HT(1A)-receptor in the hippocampus and Nac in the modulation of cocaine stimulant effects.